MTP

MTP

1. Medical Termination Of Pregnancy Dr Manjuprasad Moderator: Dr Princy Palatty

2. Overview Introduction MTP act Methods of MTP Conclusion

3. Introduction A medical abortion is brought about by taking medications that will end a pregnancy, alternative is the surgical abortion which ends a pregnancy by emptying the uterus (womb) with special instruments .

4. Hippocratic oath forbade physicians from inducing elective abortions But, Aristotle held that abortion was ethical if performed in the first trimester of pregnancy

5. Before 1971: Abortion – purposely causing miscarriage 1860 IPC under British rule – induced abortion is illegal Abortion practitioners would either be incarcerated for 3yrs or fined or both Women could be imprisoned upto 7yrs & also would be fined Only exception was abortion done to save women life

6. MTP 1971 Conditions under which a pregnancy can be terminated Who can perform such terminations The place where such terminations can be performed

7. Conditions where pregnancy can be terminated : Medical Eugenic Humanitarian Socio economic Failure of contraceptives

8. Qualification to perform abortion Assistance of atleast 25 cases of MTP in approved institution 6months of Housemanship in OB&G A PG qualification in OB&G 3yrs of practice in OBG for those doctors registered before 1971 MTP act was passed

9. Place where MTP performed Place established and maintained by Govt. Non Govt institutions can perform provided they obtain license from Chief Medical Officer of the district.

10. Consent Can only be terminated on a written informed consent of the woman, husband consent not required <18yr or lunatic – written consent of parent or legal guardian.

11. Termination is permitted upto 20wks of pregnancy When pregnancy >12 week 2medical practitioners opinion required The abortion has to be performed confidentially and reported to Director of Health Services in prescribed form

12. Methods of termination 1 st trimester Medical - Mifepristone - Mifepristone & Misoprostol - Methotrexate & Misoprostol - Tamoxifene & misoprostol Surgical – Vacuum aspiration - suction evacuation & or curettage - Dialatation and evacuation Rapid Slow

13. 2 nd trimester Prostaglandins – Misoprostol - Carboprost - Dinoprost Dilatation and evacuation – 13-14wks Intrauterine instillation of hypertonic solutions Oxytocin infusion Hysterectomy

14. Classification of drugs used in MTP

15. Mifepristone : Synthetic steroid antiprogesterone , antiglucocorticoid & antiandrogen Partial agonist, competative antagonist in presence of progesterone 80-85% effective in causing abortion

16. Blockage of the progesterone receptor results in vascular damage, decidual necrosis and bleeding

17. Mifepristone blocks progesterone receptors Endometrial decidual degeneration Trophoblast detachment ↓HCG from syncytiotrophoblast Inturn ↓ progesterone by corpus luteum

18. Pharmacological actions Decidual breakdown by blockade of uterine PR Detachment of the blastocyst which decreases hCG production Decrease in progesterone secretion from the corpus luteum increase uterine PG levels sensitizes the myometrium to their contractile actions. Cervical softening, which facilitates expulsion of the detached blastocyst

19. Pharmacokinetics Orally active with good bioavailability t 1/2 of 20-40 hrs Bound by α 1 -acid glycoprotein. Hepatic metabolism and enterohepatic circulation Metabolic products are found predominantly in the faeces

20. Contraindications : Ectopic prgnancy In presence of IUD Adrenal failure Hemorrhagic disorders Porphyria Patients on long term therapy with corticosteroids

21. Misoprostol (PGE1) Synthetic prostaglandin E1 Inexpensive and can be stored at room temperature MOA Binds to myometrial cells causes myometrial contraction and expulsion of tissues Also causes ripening of cervix

22. PHARMACOKINETICS After oral administration, rapidly absorbed from the GI tract . t1/2 20-40 mins DOSE:400 μg oral misoprostol, the plasma misoprostol level increases rapidly and peaks at about 30 minutes declines rapidly by 120 minutes and remains low thereafter. ROUTES OF ADMINISTRATION : Oral, vaginal, sublingual, buccal or rectal Mainly urinary excretion

23. Protocol 200mg of mifepristone given orally on day1 On day 3 misoprostol 400mcg PO Or 800mcg PV Patient remains in hospital for 4hrs during which expulsion occurs in 95% of cases

24. Mifepristone 200mg oral 36-48hrs later 800microgram misoprostol vaginal Then misoprostol 400microgram oral every 3hrs (4doses) Success rate is 97%

25. Gemeprost PGE1 analogue (16, 16-dimethyl-trans-d2- PGE1 methyl ester) Used as a vaginal pessary . Every 3-6hrs for 5 doses in 24hrs Has got 90% success rates Used as a non-surgical method to dilate the cervix before VA in late-first and early-second-trimester abortion SE : Vaginal bleeding, cramps, nausea, vomiting, diarrhea , headache, muscle weakness , backache ,chest pain

26. CARBOPROST Carboprost tromethamine PGF2α analogue First analogue to be tested clinically on a large scale for the termination of second trimester pregnancy. MOA- It acts on the corpus luteum to cause luteolysis , forming a corpus albicans and stopping the production of progesterone

27. Dose: IM 100-200 µg Post partum haemorrhage ADR: diarrhoea (most common) fever chills vomiting Cardiovascular collapse, Postural hypotension

28. DINOPROSTONE Synthetic derivative of PGE2 ROUTE OF ADMINISTRATION : vaginal/ oral Intravaginal suppository  20mg 3-5 hrs repeated. (17hrs ) Half life 2.5-5 mins . Excreted in urine Induction abortion in second trimester/ early abortion Cervical ripening-10mg tab / 0.5 mg gel 6 hrly SE- Prolonged vaginal bleeding, Severe menstrual cramps ,GI toxicity.

29. Methotrexate MTX is an antifolate belonging to the antimetabolite class of antineoplastic agent. MTX is a cell cycle specific chemotherapeutic agents that acts on S-phase & thus inhibit DNA synthesis

30. Pharmacokinetics Readily absorbed from the GI tract at doses of <25 mg/m 2 7-hydroxy-methotrexate NEPHROTOXIC t ½ 8 hrs IM 50% of methotrexate binds to plasma proteins Up to 90% of a given dose is excreted unchanged in the urine within 48 hours Retained in the form of polyglutamates for long periods Weeks in the kidneys and for several months in the liver

31. Methotrexate/Misoprostol Regimens Methotrexate: 50 mg/m 2 IM or 50 mg PO Misoprostol: 800 µg PV 3–7 days later Efficacy decreases after 49 days’ gestation Initial follow-up ~1 week after methotrexate Subsequent care based on results of physical exam, ultrasonography If HCG has fallen by >80% over 7days,procedure was successful

32. Contraindications Anemia ( Hgb < 10 g/ dL )/ leucopenia / thrombocytoenia Known coagulopathy Active renal or liver disease Uncontrolled seizure disorder Acute inflammatory bowel disease Intrauterine device in situ High intial hcg concentration >5000mU/ml Ectopic pregnancy > 4cm in size as in TVS

33. Regimens for medical abortion and their effectiveness Regimens Effectiveness Use upto Mifepristone + misoprostol or mifepristone + gemeprost >96% 9 weeks from last menstrual period Misoprostol alone >83% 12 weeks from last menstrual period Methotrexate + misoprostol >90% 9 weeks from last menstrual period

34. Older methods Hystrecotomy ( sectio parva ) Intra-amniotic injection of hypertonic saline/hyperosmolar urea Intra- or extra-amniotic administration of ethacryidine lactate ( Rivanol ) Parenteral/intra-amniotic / extra-amniotic administration of prostaglandin (PG) analogues I.V / i.m . administration of oxytocin

35. ETHACRIDINE LACTATE Ethacridine lactate/ Rivanol is a yellow dye with antiseptic properties MOA: Stimulates endogenous PG and thromboxane production, promoting cervical priming and initiating labour DOSE:0.1%-solution of ethacridine lactate - extra-amniotic space through a sterile catheter at a dose of 10 mL per gestational week 20-40 hrs mini labour Maximum of 150 ml

36. Hypertonic Saline One of the first described instillation methods When used alone, intra-amniotic hypertonic saline has a long latent period until the onset of contractions Time to abortion of 30 hours Addition of oxytocin to this regimen improves the efficacy and expulsion time

37. Use of concentrations exceeding 20%. Maternal hypernatremia Coagulopathy Hemorrhage Cervical laceration SIDE EFFECTS

38. IV OXYTOCIN First described by Winkler and associates 100 units per 500 mL of DNS, is infused over 3 hours The dose  is increased 50 units per 500 mL of DNS until delivery is achieved Maximum of 300 units Mean time to delivery of 8.2 hours

39. UREA Rapidly traverses cell membranes Has a long instillation to abortion interval when used alone Intra-amniotic urea, 80 to 90 g, with intravenous oxytocin Average time to expulsion of 19 to 29 hours

40. Bibliography Goodmann and Gilman’s The pharmacological basis of therapeutics 12 th edition Text Book of Obstetrics; D.C Dutta 4 th edition  Preventive and Social  Medicine   21 st Edition Udaykumar P. Medical Pharmacology . 4 th ed. New Delhi: CBS Publishers; 2013. Sharma HL, Sharma KK . Principles of Pharmacology . 2 nd ed. New Delhi: Paras Medical Publishers; 2011 . Uptodate.com Ashok PW, Templeton AA. Non-surgical mid-trimester termination of pregnancy: a review of 500 consecutive cases. Br J Obstet Gynaecol 1999;106:706 Stubblefield PG, Carr-Ellis S, Borgatta L.Methods for induced abortion. Obstet Gynecol2004;104:174-85